Effects of the adrogenic/anabolic steroid stanozolol on GABA(A) receptor function: GABA-stimulated Cl-36(-) influx and [S-35] TBPS binding

We have recently demonstrated that androgenic/anabolic steroids modulate in vitro ligand binding to the benzodiazepine binding site(s) associated with the gamma-aminobutyric acid(A) (GABA(A)) receptor complex (Masonis and McCarthy, 1995). One androgenic/anabolic steroid in particular, stanozolol, appears to stabilize the GABA(A) receptor in a moderate-affinity state for benzodiazepine binding. In the present study, we demonstrate the effects of stanozolol on the functional responsiveness of the GABA(A) receptor. After pre-incubation with stanozolol, we observed a decrease in the E(max) and EC(50) values for GABA-stimulated Cl-36(-) influx into cortical synaptoneurosomes. Moreover, in the presence of stanozolol, flunitrazepam-enhanced GABA-stimulated Cl-36(-) influx was lost, and the GABA(A) receptor was stabilized in a functional state that was resistant to further desensitization by agonist. Stanozolol does not appear to reduce GABA-stimulated Cl-36(-) influx by acting as a channel blocker at the well-characterized channel blocker binding site, as illustrated by the GABA-sensitive biphasic effects of stanozolol on [S-35] t-butylbicyclophosphorothionate binding. These results demonstrate a novel, nongenomic mechanism for androgenic/anabolic steroidal modulation of CNS function.